Most forms of reversible contraception are practiced by the female member of an animal pair, whether the animal be human or not. With humans, physical (diaphragm and IUD) and chemical ("the Pill", vaginal creams, foams, ointments, etc.) methods are available. At present there are only two acceptable methods for the human male. These are the condom and bilateral vasectomy. With the condom the failure rate is high, resulting in unwanted pregnancies. Vasectomies for practical purposes must be considered irreversible. Therefore, a method of male human contraception which is both reversible and reliable is highly desirable.
With regards to the non-human mammals a male contraceptive is also highly desirable. For non-domestic commercial animals such as horses, cattle, sheep, etc., the present situation is to separate male and female animals so the female may be selectively, artificially inseminated. It would, of course, be simpler to permit the animals to cohabitate under circumstances where the female cannot become pregnant. Domestic animals normally cohabitate because it is virtually impossible to separate male and female cats and dogs in a household. Many times it would be desirable to be able to prevent unwanted pregnancies of domestic animals under cohabitation circumstances. Additionally, with undesirable rodents a male contraceptive would be helpful to decrease breeding and thereby decrease or eliminate the undesirable rodents.
E. Steinberger et al., Fertility and Sterility 27, 216 (1976), reported azoospermia in men who acknowledged paternity, by administration of testosterone enanthate. J. Mauss et al., Acta. Endocrinol. 78, 373 (1975) reported testosterone enanthate reduced the sperm count of seven men to less than 3,000,000 sperm/ml. Testosterone and testosterone enanthate are not within the scope of the compounds of the present invention because they are androgenic and the users would experience the known side effects of androgens including prostate enlargement, seminal vesicle enlargement, excess and unwanted hair growth and behavioral disturbances. The steroids within the scope of the present invention are much less androgenic as defined by these classical measures of androgenicity and by the ABP/AR ratio.
Howard C. Morse et al., J. Clin. Endocrinol. Metab., 37, 882 (1973) reported administering testosterone propionate to six normal men and found a decrease in testicular testosterone as well as a sharp drop in sperm concentration. Not only is testosterone propionate not within the scope of the present invention, but the publication does not even infer that the sperm level is decreased to the point that testosterone propionate is a contraceptive agent.
C. A. Paulsen and John M. Leonard, in Clinical Trials in Reversible Male Contraception: I, Combination of Danazol Plus Testosterone in Regulatory Mechanisms of Male Reproductive Physiology, C. H. Spilman et al., Editors, Excerpta Medica, Amsterdam, 1976, page 197 describe a Danazol-testosterone combination which ". . . represents a viable pathway for the purpose of inducing a reversible state of male infertility." Testosterone is known to produce undesired androgenic side effects.
U.S. Pat. No. 3,655,889 discloses a method of controlling the propagation of rodents by oral administration of quinesterol to both males and females. Quinesterol, an estrogen-type (aromatic A ring) steroid, is not within the scope of the present invention which utilizes non-estrogenic-type steroids (A ring is not aromatic).
U.S. Pat. No. 3,873,701 discloses using O-aryl oximes of testosterone-type compounds post-coitally in the female for suppression of reproduction. The compounds of the present invention are used in the male prior to sexual intercourse.
U.S. Pat. No. 4,000,273 discloses the use of 7.alpha.-methylestr-4-ene-3.alpha.,17.beta.-diol-type compounds to reduce fertility in female mammals. The present invention involves contraceptives in males.
U.S. Pat. No. 3,846,456 discloses the use of various 2.alpha.,7.alpha.-dimethyltestosterone-type steroids for various uses including anti-fertility. However, these compounds have substantial androgenic side effects. The male contraceptive steroids of the present invention have minimal androgenic side effects (low affinity for AR). 2.alpha.,7.alpha.-Dimethyltestosterone had an ABP/AR ratio of about 6.0.